Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division
Alice Grob, Christine Colleran, and Brian McStay
This study investigates the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleoli disappear during mitosis and reform around nucleolar organizer regions (NORs). By examining the effects of Pol I transcription factor UBF depletion on endogenous NORs and synthetic neo-NORs, we show that UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly. This study not only reveals that nucleolar assembly is a staged process but also establishes the sequence requirements for nucleolar biogenesis.
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The shared genomic architecture of human nucleolar organizer regions
Ioanna Floutsakou, Saumya Agrawal, Thong T. Nguyen, Cathal Seoighe, Austen R.D. Ganley, and Brian McStay
Here we describe the genomic architecture of human nucleolar organizers. Sequences distal and proximal to ribosomal gene arrays are conserved among the acrocentric chromosomes. Although previously believed to be heterochromatic, characterization of these two flanking regions reveals that they share a complex genomic architecture. Proximal sequences are almost entirely segmentally duplicated, similar to the regions bordering centromeres. In contrast, the distal sequence is predominantly unique to the acrocentric short arms and is dominated by a very large inverted repeat. We show that the distal element is localized to the periphery of the nucleolus, where it appears to anchor the ribosomal gene repeats. This, combined with its complex chromatin structure and transcriptional activity, suggests that this region is involved in nucleolar organization.
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